Shikimic acid is useful as starting materials for antibacterial, antifungal, herbicidal agents and as nutritional. Originally shikimic acid was isolated from Japanese star anise (Botanical name—Illicium anise family—Illiciaceae) in trace amount. Later on, it was found to occur in many plants in very trace amount. Then, it was found that shikimic acid is an intermediate metabolite in the common or shikimate pathway of plants and microorganisms. However, only two plant species of the world are found to accumulate this polyhydroxy aromatic acid in more amount, namely in seeds of Star Anise (Botanical name Illicium verum, family—Illiciaceae) and Sweet gum tree (Botanical Name—Liquidambar styraciflu). Although, there are 42 species of the genus Illicium are available in nature, only one species (i.e. Illicium verum) is useful for the production of shikimic acid with a yield of maximum 7% w/w.
I. griffithii (Hook. f. & Thorns.) belongs to family Illiciaceae, and is one of the most frequently occurring Illicium species in the world. In Arunachal Pradesh, it is locally known as ‘Lissi’. It is a small to medium sized tree, which occurs in subtropical and temperate broad-leaved forests of West Kameng, Tawang, Lohit and Lower Subansiri districts and is widely distributed in Bomdila, West Kameng district. Fruits of I. griffithii are used in the spice industries. (Reference: R. Duchok, K. Kent, A. Devi Khumbongmayum, A. Paul and M. L. Khan; Population structure and regeneration status of medicinal tree Illicium griffithii in relation to disturbance gradients in temperate broad-leaved forest of Arunachal Pradesh; Current Science, Vol. 89, No. 4, 25 August 2005, page 673)
References may be made to U.S. Pat. No. 3,546,072, wherein Araki et al. discloses that 5-dehydroshikimic acid can be prepared by culturing a 5-dehydroshikimic acid producing microorganism of the genus Corynebacterium in a culture medium (fermentation broth), containing a carbon source, a nitrogen source, inorganic material and nutrients. The produced and accumulated 5-dehydroshikimic acid is isolated from the culture medium, after filtration to remove the microbial cells, through an adjustment of pH and the addition of active carbon. The active carbon absorbs the 5-dehydroshikimic acid and is eluted with 98% ethanol. The eluate is concentrated under reduced pressure and then the product precipitated from ethanol. This reference does not suggest or disclose the use of an organic acid such as acetic acid to enhance the precipitation of highly pure shikimic acid crystals from an aqueous fermentation broth.
References may be made to U.S. Pat. No. 4,769,061, wherein Comai discloses a genetically modified plant wherein a gene encoding for a mutated glyphosate resistant 5-enolpyruvyl-3-phosphoskimimate synthase enzyme is included in the genome of the plant. This reference makes no suggestion of how to isolate shikimic acid from the tissue of such a genetically modified plant.
References may be made to U.S. Pat. No. 5,214,165, wherein Sutherland et al. relates to 6-fluoroshikimic acid derivatives that have antibacterial, antifungal and herbicidal activity. This reference does not suggest the use of genetically modified microorganisms nor the use of glyphosate addition to a fermentation process to increase the production of shikimic acid. This reference further fails to suggest the use of an organic acid to assist in the isolation of shikimic acid from a fermentation broth. This reference does, however, disclose a class of PCCAs that are useful in the process of this invention.
References may be made to U.S. Pat. No. 5,605,818, wherein Katsumata et al. discloses a process for producing an aromatic amino acid, such as tryptophan, through the use of culturing in a medium a mutant strain of the genus Corynebacterium or Brevibacterium. 
These mutant strains are capable of producing the desired aromatic amino acid and also have a higher transketolase activity than that of the parent strain. The desired aromatic amino acid is accumulated in the culture and recovered therefrom. This reference makes no suggestion of the use of an organic acid to isolate the desired PCCA from the broth. This reference does disclose a number of microorganisms that may produce a fermentation broth that is useful in the present invention.
References may be made to article entitled “Recovery of shikimic acid using temperature-swing complexation extraction and displacement back extraction” in Isolation & Purification, 1994, Vol. 2, pp. 75-82, wherein Miles et al. discloses a process for the removal of shikimic acid from aqueous solutions. The Miles et al. process is accomplished through solvent extraction using tridodecylamine dissolved in n-heptanol or n-butanol and back extraction to water using oleic acid to displace the shikimic acid from the organic phase. This reference focuses on developing a general method for recovering metabolic acids from fermentation broths. It fails, however, to disclose the use of acetic acid, which is added to a concentrated fermentation broth, to enhance the precipitation of shikimic acid from the broth.
An article from Synthesis of February, 1993 entitled: “The Biosynthesis and Synthesis of Shikimic Acid, Chorismic Acid and Related Compounds”, pp. 179-193 by Campbell et al. teaches that compounds other than glyphosate may interfere, with the shikimic acid pathway. This article also provides a good description of the glucose derived shikimate pathway and the various arduous approaches to the chemical synthesis of shikimic acid. This article makes no suggestion regarding the isolation of highly pure PCCA from reaction mixtures through the use of concentrated acetic, lactic and/or propionic acids.
References may be made to Journal entitled: “Chemical Synthesis of Shikimic Acid and Its Analogues” in Tetrahedron Report Number 449, Vol. 54 (1998), pp. 4697-4753, wherein Jiang, et al. disclosed the complex and arduous task of the synthesis of shikimic acid and its analogues. Jiang, et al., like Campbell, et al, fails to disclose the present invention.
References may be made to U.S. Pat. No. 6,794,164, wherein Malmberg et al discloses a invention that has directed to the use of crystallization in acids, such as acetic, lactic and propionic acids, to obtain high purity polyhydroxylcyclic carboxylic acids (PCCA) from low purity aqueous solutions. The preferred PCCA is shikimic acid and the preferred crystallization acid is acetic acid. The method according to the invention is particularly applicable to the isolation of shikimic acid from a fermentation broth.
References may be made to patent application US20030138920, wherein Malmberg et al discloses an invention entitled Process for the isolation of polyhydroxy cyclic carboxylic acids. This invention is directed to the use of crystallization acids, such as acetic, lactic and propionic acids, to obtain high purity polyhydroxylcyclic carboxylic acids (PCCA) from low purity aqueous solutions. The preferred PCCA is shikimic acid and the preferred crystallization acid is acetic acid. The method according to the invention is particularly applicable to the isolation of shikimic acid from a fermentation broth.
In a report published in a web based encyclopaedia www.en.wikipedia.com, shikimic acid is extracted normally from chinese star anise with a yield of 3-7%. As found in the same report, another source of shikimic acid is seeds of sweetgum fruit found abundantly in North America, the yield of shikimic acid from this source are only 1.5%,
Reference may also be made to the published report [Shende Jiang and Gurdial Singh, Chemical Synthesis of Shikimic Acid and Its Analogues, Tetrahedron report number 449, Tetrahedron 54 (1998) 4697-4753] wherein various methods of chemical synthesis of shikimic acid and its analogues are described. However, these methods are not suitable due to low yield and high cost of production.
In the pharmaceutical industry, shikimic acid from the Chinese star anise is used almost exclusively as a base material for production of Tami flu (oseltamivir). Tamiflu is the only drug available for the treatment of bird flu disease caused by avian influenza virus H5N1. Currently Tamiflu is produced starting from shikimic acid according to a technology Roche of Switzarland. Currently, due to recent outbreak of avian flu, tamiflu is required in 65 countries worldwide. Every year, it is estimated, required tamiflu will worth from Swiss franc 1.1 billion to 1.2 billion. (David Bradley, Star role for bacteria in controlling flu pandemic? Nature Reviews Drug Discovery, 2005, 4 (12), 945-946).
It is reported that triacyl shikimic acid derivatives can inhibit blood platelet assembling and Thrombosis by affecting the metabolism of Arachidonic acid (F. Huang; Q. Xiu; J. G Sun; H. Enrique; Anti-platelet and anti-thrombotic effects of triacetylshikimic acid in rats; Journal of cardiovascular pharmacology, 2002, vol. 39, No 2, pp. 262-270). According to a report in http://en.wikipedia.org/wiki/Shikimic_acid, in the pharmaceutical industry, shikimic acid from the Chinese star anise is used as a base material for production of Tamiflu (oseltamivir). Although shikimic acid is present in most autotrophic organisms, it is a biosynthetic intermediate and generally found in very low concentrations. The low isolation yield of shikimic acid from the Chinese star anise is responsible for the 2005 shortage of oseltamivir. Shikimic acid can also be extracted from the seeds of the sweetgum fruit (Liquidambar styraciflua), which is abundant in North America, in yields of around 1.5%, so just 4 kg of sweetgum seeds are enough for fourteen packages of Tamiflu. By comparison star anise has been reported to yield 3 to 7% shikimic acid. Recently biosynthetic pathways in E. coli have been enhanced to allow the organism to accumulate enough material to be used commercially (David Bradley, Star role for bacteria in controlling flu pandemic Nature Reviews Drug Discovery, 2005, 4 (12), 945-946).
According to a report published at the website www.livemint.com, China Government has currently imposed restriction on export of shikimic acid.
According to report the chemical composition of essential oils from several parts of a type of Illicium griffithii (short peduncle) harvested in Vietnam was investigated using GC, GC/MS and 13C-NMR spectroscopy. These oils contained mostly oxygenated phenylpropanoids, essentially safrole (51.6-65.3%) and 4-methoxysafrole (19.6%, root bark oil). Oils from aerial parts and bark of root oil differed significantly (Journal of Essential Oil Research: JEOR, January/February 2005 by Tam, Nguyen Thi, An, Ha Lai, Bighelli, Ange, Muselli, Alain, Casanova, Joseph).
Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) has three (3) chiral centers, which make six (6) different optical isomers possible. A preferred product produced according to the present invention is the natural levorotatory L-shikimic acid of the structural formula 1.

Shikimic acid is an important new metabolic nutritional and starting material for antiviral, antibacterial and other therapeutic agents. While shikimic acid can be synthesized using various chemical routes, it is costly and presents difficulty in obtaining the proper stereoisomer. The compound can also be extracted from microorganism fermentation broth, but clean up and obtaining the high level of purity required is also problematic from this source. Present invention provides a method for the production of shikimic acid useful as raw material for the production of triacyl shikimic acid derivatives which can inhibit blood platelet assembling and Thrombosis by affecting the metabolism of Arachidonic acid. Present invention provides an alternative and commercially useful method than the hitherto known commercial methods of production of shikimic acid from the fruits of star anise (Illicium verum) and sweet gum (Liquidambar styraciflua) gives only 3-7% and 1.5% yield respectively. The process for obtaining shikimic acid from Illicium griffithii has been shown to be cost effective and practical. One aspect of the present invention provides an effective means to obtain high purity shikimic acid crystals from a crude aqueous alcoholic solution of shikimic acid. The process does not need the use of any acids, or elaborate temperature-swing complexation extractions and displacement back extractions.